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Repeat Radiosurgery for Sporadic Vestibular Schwannoma After Primary Radiosurgical Failure: An International Multi-institutional Investigation

Khandalavala, Karl R; Herberg, Hans A; Kay-Rivest, Emily; Moore, Lindsay S; Yancey, Kristen L; Marinelli, John P; Lund-Johansen, Morten; Kosaraju, Nikitha; Lohse, Christine M; Kutz, Walter; Santa Maria, Peter L; Golfinos, John G; Kondziolka, Douglas; Carlson, Matthew L; Tveiten, Øystein V; Link, Michael J
OBJECTIVE:To describe outcomes of patients with sporadic vestibular schwannoma (VS) who underwent repeat stereotactic radiosurgery (SRS) after primary SRS failure. STUDY DESIGN/METHODS:Multi-institutional historical cohort study. SETTING/METHODS:Five tertiary care referral centers. PATIENTS/METHODS:Adults ≥18 years old with sporadic VS. INTERVENTION/METHODS:Primary and repeat treatment with SRS. MAIN OUTCOME MEASURE/METHODS:Microsurgery-free survival after repeat SRS. RESULTS:Across institutions, 32 patients underwent repeat SRS after primary SRS. Most patients (74%) had tumors with cerebellopontine angle extension at primary SRS (median size, 13.5 mm [interquartile range, 7.5-18.8] mm). After primary SRS, patients underwent repeat SRS at a median of 4.8 years (interquartile range, 3.2-5.7 yr). For treatment modality, 30 (94%) patients received gamma knife for primary treatment and 31 (97%) patients received gamma knife as their repeat treatment. Median tumor volume increased from 0.970 cm3 at primary SRS to 2.200 cm3 at repeat SRS. Facial nerve function worsened in two patients after primary SRS and in two patients after repeat SRS. There were no instances of intracranial complications after repeat SRS. Microsurgery-free survival rates (95% confidence interval; number still at risk) at 1, 3, and 5 years after repeat SRS were 97% (90-100%, 24), 84% (71-100%, 13), and 68% (48-96%, 6), respectively. There was one occurrence of malignancy diagnosed after repeat radiosurgery. CONCLUSION/CONCLUSIONS:Overall, repeat SRS for sporadic VS has comparable risk profile, but lower rates of tumor control, compared with primary SRS.
PMID: 38728563
ISSN: 1537-4505
CID: 5656062

Improved outcomes for triple negative breast cancer brain metastases patients after stereotactic radiosurgery and new systemic approaches

Mashiach, Elad; Alzate, Juan Diego; De Nigris Vasconcellos, Fernando; Adams, Sylvia; Santhumayor, Brandon; Meng, Ying; Schnurman, Zane; Donahue, Bernadine R; Bernstein, Kenneth; Orillac, Cordelia; Bollam, Rishitha; Kwa, Maryann J; Meyers, Marleen; Oratz, Ruth; Novik, Yelena; Silverman, Joshua S; Harter, David H; Golfinos, John G; Kondziolka, Douglas
PURPOSE/OBJECTIVE:Although ongoing studies are assessing the efficacy of new systemic therapies for patients with triple negative breast cancer (TNBC), the overwhelming majority have excluded patients with brain metastases (BM). Therefore, we aim to characterize systemic therapies and outcomes in a cohort of patients with TNBC and BM managed with stereotactic radiosurgery (SRS) and delineate predictors of increased survival. METHODS:We used our prospective patient registry to evaluate data from 2012 to 2023. We included patients who received SRS for TNBC-BM. A competing risk analysis was conducted to assess local and distant control. RESULTS:Forty-three patients with 262 tumors were included. The median overall survival (OS) was 16 months (95% CI 13-19 months). Predictors of increased OS after initial SRS include Breast GPA score > 1 (p < 0.001) and use of immunotherapy such as pembrolizumab (p = 0.011). The median time on immunotherapy was 8 months (IQR 4.4, 11.2). The median time to new CNS lesions after the first SRS treatment was 17 months (95% CI 12-22). The cumulative rate for development of new CNS metastases after initial SRS at 6 months, 1 year, and 2 years was 23%, 40%, and 70%, respectively. Thirty patients (70%) underwent multiple SRS treatments, with a median time of 5 months (95% CI 0.59-9.4 months) for the appearance of new CNS metastases after second SRS treatment. CONCLUSIONS:TNBC patients with BM can achieve longer survival than might have been previously anticipated with median survival now surpassing one year. The use of immunotherapy is associated with increased median OS of 23 months.
PMID: 38630386
ISSN: 1573-7373
CID: 5655852

Vestibular Schwannoma International Study of Active Surveillance Versus Stereotactic Radiosurgery: The VISAS Study

Bin-Alamer, Othman; Abou-Al-Shaar, Hussam; Peker, Selcuk; Samanci, Yavuz; Pelcher, Isabelle; Begley, Sabrina; Goenka, Anuj; Schulder, Michael; Tourigny, Jean-Nicolas; Mathieu, David; Hamel, Andréanne; Briggs, Robert G; Yu, Cheng; Zada, Gabriel; Giannotta, Steven L; Speckter, Herwin; Palque, Sarai; Tripathi, Manjul; Kumar, Saurabh; Kaur, Rupinder; Kumar, Narendra; Rogowski, Brandon; Shepard, Matthew J; Johnson, Bryan A; Trifiletti, Daniel M; Warnick, Ronald E; Dayawansa, Samantha; Mashiach, Elad; Vasconcellos, Fernando De Nigris; Bernstein, Kenneth; Schnurman, Zane; Alzate, Juan; Kondziolka, Douglas; Sheehan, Jason P
PURPOSE/OBJECTIVE:The present study assesses the safety and efficacy of stereotactic radiosurgery (SRS) versus observation for Koos grade 1 and 2 vestibular schwannoma (VS), benign tumors affecting hearing and neurological function. METHODS AND MATERIALS/METHODS:This multicenter study analyzed data from Koos grade 1 and 2 VS patients managed with SRS (SRS group) or observation (observation group). Propensity score matching balanced patient demographics, tumor volume, and audiometry. Outcomes measured were tumor control, serviceable hearing preservation, and neurological outcomes. RESULTS:In 125 matched patients in each group with a 36-month median follow-up (P = .49), SRS yielded superior 5- and 10-year tumor control rates (99% CI, 97.1%-100%, and 91.9% CI, 79.4%-100%) versus observation (45.8% CI, 36.8%-57.2%, and 22% CI, 13.2%-36.7%; P < .001). Serviceable hearing preservation rates at 5 and 9 years were comparable (SRS 60.4% CI, 49.9%-73%, vs observation 51.4% CI, 41.3%-63.9%, and SRS 27% CI, 14.5%-50.5%, vs observation 30% CI, 17.2%-52.2%; P = .53). SRS were associated with lower odds of tinnitus (OR = 0.39, P = .01), vestibular dysfunction (OR = 0.11, P = .004), and any cranial nerve palsy (OR = 0.36, P = .003), with no change in cranial nerves 5 or 7 (P > .05). Composite endpoints of tumor progression and/or any of the previous outcomes showed significant lower odds associated with SRS compared with observation alone (P < .001). CONCLUSIONS:SRS management in matched cohorts of Koos grade 1 and 2 VS patients demonstrated superior tumor control, comparable hearing preservation rates, and significantly lower odds of experiencing neurological deficits. These findings delineate the safety and efficacy of SRS in the management of this patient population.
PMID: 38588868
ISSN: 1879-355x
CID: 5657262

Stereotactic radiosurgery for non-functioning pituitary tumor: a multicenter study of new pituitary hormone deficiency

Dumot, Chloe; Mantziaris, Georgios; Dayawansa, Sam; Peker, Selcuk; Samanci, Yavuz; Nabeel, Ahmed M; Reda, Wael A; Tawadros, Sameh R; AbdelKarim, Khaled; El-Shehaby, Amr M N; Emad, Reem M; Abdelsalam, Ahmed Ragab; Liscak, Roman; May, Jaromir; Mashiach, Elad; De Nigris Vasconcellos, Fernando; Bernstein, Kenneth; Kondziolka, Douglas; Speckter, Herwin; Mota, Ruben; Brito, Anderson; Bindal, Shray Kumar; Niranjan, Ajay; Lunsford, L Dade; Benjamin, Carolina Gesteira; Abrantes de Lacerda Almeida, Timoteo; Mao, Jennifer; Mathieu, David; Tourigny, Jean-Nicolas; Tripathi, Manjul; Palmer, Joshua David; Matsui, Jennifer; Crooks, Joe; Wegner, Rodney E; Shepard, Matthew J; Vance, Mary Lee; Sheehan, Jason P
BACKGROUND:Stereotactic radiosurgery (SRS) is used to treat recurrent or residual nonfunctioning pituitary neuroendocrine tumors (NFPA). The objective of the study was to assess imaging and development of new pituitary hormone deficiency. METHODS:Patients treated with single-session SRS for a NFPA were included in this retrospective, multicenter study. Tumor control and new pituitary dysfunction were evaluated using Cox analysis and Kaplan-Meier curves. RESULTS:869 patients (male 476 [54.8%], median age at SRS 52.5 years [Interquartile range (IQR):18.9]) were treated using a median margin dose of 14Gy (IQR:4) for a median tumor volume of 3.4 cc (IQR: 4.3). With a median radiological follow-up of 3.7 years (IQR: 4.8), volumetric tumor reduction occurred in 451 patients (51.9%), stability in 364 (41.9%) and 54 patients (6.2%) showed tumor progression.The probability of tumor control was 95.5% (95% Confidence Interval [CI]: 93.8-97.3) and 88.8% (95%CI: 85.2-92.5) at 5 and 10 years, respectively. A margin dose >14 Gy was associated with tumor control (Hazard Ratio HR:0.33 [95%CI:0.18-0.60], p<0.001).The probability of new hypopituitarism was 9.9% (95% CI: 7.3-12.5) and 15.3% (95% CI:11-19.4) at 5 and 10 years, respectively.A maximum point dose >10 Gy in the pituitary stalk was associated with new pituitary hormone deficiency (HR:3.47, 95% CI:1.95-6.19). The cumulative probability of new cortisol, thyroid, gonadotroph and growth hormone deficiency was 8% (95% CI:3.9-11.9), 8.3% (95% CI:3.9-12.5), 3.5% (95% CI:1.7-5.2), and 4.7% (95% CI:1.9-7.4), respectively at 10 years. CONCLUSION/CONCLUSIONS:SRS provides long-term tumor control with a 15.3% risk of hypopituitarism at 10 years.
PMID: 38095431
ISSN: 1523-5866
CID: 5589352

Impact of Multiple Sclerosis Subtypes on Pain Management in Patients With Trigeminal Neuralgia After Stereotactic Radiosurgery: An International Multicenter Analysis

De Nigris Vasconcellos, Fernando; Mashiach, Elad; Alzate, Juan Diego; Bernstein, Kenneth; Rotman, Lauren; Levy, Sarah; Qu, Tanxia; Wegner, Rodney E; Shepard, Matthew J; Patel, Samir; Warnick, Ronald E; Moreno, Nuria Martínez; Martínez Álvarez, Roberto; Picozzi, Piero; Franzini, Andrea; Peker, Selçuk; Samanci, Yavuz; Elguindy, Ahmed N; Palmer, Joshua D; Lunsford, L Dade; Jose, Shalini G; Wei, Zhishuo; Niranjan, Ajay; Blagui, Sarra; Iorio-Morin, Christian; Mathieu, David; Briggs, Robert G; Yu, Cheng; Zada, Gabriel; Dayawansa, Samantha; Sheehan, Jason; Schulder, Michael; Goenka, Anuj; Begley, Sabrina; Khilji, Hamza; Urgošík, Dušan; Liščák, Roman; Kondziolka, Douglas
BACKGROUND AND OBJECTIVES/OBJECTIVE:Trigeminal neuralgia affects approximately 2% of patients with multiple sclerosis (MS) and often shows higher rates of pain recurrence after treatment. Previous studies on the effectiveness of stereotactic radiosurgery (SRS) for trigeminal neuralgia did not consider the different MS subtypes, including remitting relapsing (RRMS), primary progressive (PPMS), and secondary progressive (SPMS). Our objective was to investigate how MS subtypes are related to pain control (PC) rates after SRS. METHODS:We conducted a retrospective multicenter analysis of prospectively collected databases. Pain status was assessed using the Barrow National Institute Pain Intensity Scales. Time to recurrence was estimated through the Kaplan-Meier method and compared groups using log-rank tests. Logistic regression was used to calculate the odds ratio (OR). RESULTS:Two hundred and fifty-eight patients, 135 (52.4%) RRMS, 30 (11.6%) PPMS, and 93 (36%) SPMS, were included from 14 institutions. In total, 84.6% of patients achieved initial pain relief, with a median time of 1 month; 78.7% had some degree of pain recurrence with a median time of 10.2 months for RRMS, 8 months for PPMS, 8.1 months for SPMS (P = .424). Achieving Barrow National Institute-I after SRS was a predictor for longer periods without recurrence (P = .028). Analyzing PC at the last available follow-up and comparing with RRMS, PPMS was less likely to have PC (OR = 0.389; 95% CI 0.153-0.986; P = .047) and SPMS was more likely (OR = 2.0; 95% CI 0.967-4.136; P = .062). A subgroup of 149 patients did not have other procedures apart from SRS. The median times to recurrence in this group were 11.1, 9.8, and 19.6 months for RRMS, PPMS, and SPMS, respectively (log-rank, P = .045). CONCLUSION/CONCLUSIONS:This study is the first to investigate the relationship between MS subtypes and PC after SRS, and our results provide preliminary evidence that subtypes may influence pain outcomes, with PPMS posing the greatest challenge to pain management.
PMID: 38051068
ISSN: 1524-4040
CID: 5595452

Unveiling the Spectrum: Exploring the Influence of Multiple Sclerosis Subtypes in Trigeminal Neuralgia Patients Undergoing Stereotactic Radiosurgery and Beyond [Letter]

De Nigris Vasconcellos, Fernando; Mashiach, Elad; Alzate, Juan Diego; Santhumayor, Brandon; Bernstein, Kenneth; Kondziolka, Douglas
PMID: 38368151
ISSN: 1878-8769
CID: 5636182

Long-term radiographic and endocrinological outcomes of stereotactic radiosurgery for recurrent or residual nonfunctioning pituitary adenomas

Shaaban, Ahmed; Dumot, Chloé; Mantziaris, Georgios; Dayawansa, Sam; Peker, Selcuk; Samanci, Yavuz; Nabeel, Ahmed M; Reda, Wael A; Tawadros, Sameh R; Abdel Karim, Khaled; El-Shehaby, Amr M N; Emad Eldin, Reem M; Ragab Abdelsalam, Ahmed; Liscak, Roman; May, Jaromir; Mashiach, Elad; De Nigris Vasconcellos, Fernando; Bernstein, Kenneth; Kondziolka, Douglas; Speckter, Herwin; Mota, Ruben; Brito, Anderson; Bindal, Shray K; Niranjan, Ajay; Lunsford, L Dade; Benjamin, Carolina Gesteira; Almeida, Timoteo; Mao, Jennifer Z; Mathieu, David; Tourigny, Jean-Nicolas; Tripathi, Manjul; Palmer, Joshua David; Matsui, Jennifer; Crooks, Joseph; Wegner, Rodney E; Shepard, Matthew J; Sheehan, Jason P
OBJECTIVE:Stereotactic radiosurgery (SRS) is used for the treatment of residual/recurrent nonfunctional pituitary adenoma (NFPA). The aim of this study was to evaluate the factors related to long-term tumor control and delayed endocrinopathies following SRS. METHODS:This retrospective, multicenter study included patients with recurrent/residual NFPA treated with single-fraction SRS; they were then divided into two arms. The first arm included patients with at least 5 years of radiographic follow-up and all patients with local tumor progression. The second arm included patients with at least 5 years of endocrinological follow-up and all patients who developed endocrinopathy. Study endpoints were tumor control and new or worsening hypopituitarism after SRS and were analyzed using Cox regression and Kaplan-Meier methodology. RESULTS:There were 360 patients in the tumor control arm (median age 52.7 [IQR 42.9-61] years, 193 [53.6%] males) and 351 patients in the hypopituitarism arm (median age 52.5 [IQR 43-61] years, 186 [53.0%] males). The median follow-up in the tumor control evaluation group was 7.95 (IQR 5.7-10.5) years. Tumor control rates at 5, 8, 10, and 15 years were 93% (95% CI 90%-95%), 87% (95% CI 83%-91%), 86% (95% CI 82%-90%), and 69% (95% CI 59%-81%), respectively. The median follow-up in the endocrinopathy evaluation group was 8 (IQR 5.9-10.7) years. Pituitary function preservation rates at 5, 8, 10, and 15 years were 83% (95% CI 80%-87%), 81% (95% CI 77%-85%), 78% (95% CI 74%-83%), and 71% (95% CI 63%-79%), respectively. A margin dose > 15 Gy (HR 0.8, 95% CI 0.7-0.9; p < 0.001) and a delay from last resection to SRS > 1 year (HR 0.9, 95% CI 0.7-0.9; p = 0.04) were significant factors related to tumor control in multivariable analysis. A maximum dose to the pituitary stalk ≤ 10 Gy (HR 1.1, 95% CI 1.09-1.2; p < 0.001) was associated with pituitary function preservation. New visual deficits after SRS occurred in 7 (1.94%) patients in the tumor control group and 8 (2.3%) patients in the endocrinopathy group. Other new cranial nerve deficits post-SRS occurred in 4 of 160 patients with data in the tumor control group and 3 of 140 patients with data in the endocrinopathy group. CONCLUSIONS:SRS affords favorable and durable tumor control for the vast majority of NFPAs. Post-SRS hypopituitarism occurs in a minority of patients, but this risk increases with time and warrants long-term follow-up.
PMID: 38518285
ISSN: 1933-0693
CID: 5640862

Pushing the Boundaries: Long-term Survival from Brain Metastases and the Path Ahead [Letter]

Mashiach, Elad; Alzate, Juan Diego; Schnurman, Zane; Berger, Assaf; De Nigris Vasconcellos, Fernando; Golfinos, John G; Kondziolka, Douglas
PMID: 38521224
ISSN: 1878-8769
CID: 5641132

Outcomes of Gamma Knife Radiosurgery for Brain Metastases in the Motor Cortex

Prasad, Shefalika; Alzate, Juan Diego; Mullen, Reed; Bernstein, Kenneth; Qu, Tanxia; Silverman, Joshua; Kondziolka, Douglas
BACKGROUND AND OBJECTIVES/OBJECTIVE:To study the clinical, imaging, and survival outcomes in patients with motor cortex brain metastases treated with stereotactic radiosurgery (SRS). METHODS:Imaging and clinical data were obtained from our prospective patient registry. Tumor volumes were obtained from serial imaging data. RESULTS:The outcomes of 208 patients with metastases involving the motor cortex who underwent SRS between 2012 and 2021 were analyzed. A total of 279 metastases (0.01 cm3-12.18 cm3, mean 0.74 cm3) were irradiated. The SRS margin dose varied from 10 to 20 Gy (mean 16.9 Gy). The overall tumor control rate was 97.8%. Perilesional edema was noted in 69 (25%) tumors at presentation. Adverse radiation effects (ARE) were noted in 6% of all tumors but were symptomatic in only 1.4%. Median time to appearance of symptomatic ARE was 8 months. Edema without ARE was observed in 13%. New focal seizures were noted in 5 patients (2%) and new generalized seizures in 1 patient (0.3%). Thirty-six patients (17%) presented with motor deficits. At final follow-up, 32 (85%) were improved or unchanged, 13 (41%) had a normal examination, 10 (31%) had mild deficits, and 9 (28%) still had moderate deficits. New remote brain metastases were found in 31% of patients at a median of 8 months. After treatment, the Karnofsky performance score distribution of the population showed an overall right shift and a median survival of 10 months. Patients with incidentally found brain metastases had significantly better survival than those presenting with deficits (median 13 vs 9 months) (P = .048). Absence of a neurological deficit, recursive partitioning analysis Class I and II, and dose >18 Gy were each associated with a significant survival advantage. CONCLUSION/CONCLUSIONS:SRS for motor cortex metastases is safe in most patients and effective in providing tumor control. Patients treated before neurological deficits develop show better outcomes.
PMID: 37823677
ISSN: 1524-4040
CID: 5604472

The relevance of biologically effective dose for pain relief and sensory dysfunction after Gamma Knife radiosurgery for trigeminal neuralgia: an 871-patient multicenter study

Warnick, Ronald E; Paddick, Ian; Mathieu, David; Adam, Elizabeth; Iorio-Morin, Christian; Leduc, William; Hamel, Andréanne; Johnson, Sarah E; Bydon, Mohamad; Niranjan, Ajay; Lunsford, L Dade; Wei, Zhishuo; Waite, Kaitlin; Jose, Shalini; Peker, Selcuk; Samanci, Mustafa Yavuz; Tek, Ece; Mantziaris, Georgios; Pikis, Stylianos; Sheehan, Jason P; Tripathi, Manjul; Kumar, Narendra; Alzate, Juan Diego; Bernstein, Kenneth; Ahorukomeye, Peter; Kshettry, Varun R; Speckter, Herwin; Hernandez, Wenceslao; Urgošík, Dušan; Liščák, Roman; Yang, Andrew I; Lee, John Y K; Patel, Samir; Kusyk, Dorian M; Shepard, Matthew J; Kondziolka, Douglas
OBJECTIVE:Recent studies have suggested that biologically effective dose (BED) is an important correlate of pain relief and sensory dysfunction after Gamma Knife radiosurgery (GKRS) for trigeminal neuralgia (TN). The goal of this study was to determine if BED is superior to prescription dose in predicting outcomes in TN patients undergoing GKRS as a first procedure. METHODS:This was a retrospective study of 871 patients with type 1 TN from 13 GKRS centers. Patient demographics, pain characteristics, treatment parameters, and outcomes were reviewed. BED was compared with prescription dose and other dosimetric factors for their predictive value. RESULTS:The median age of the patients was 68 years, and 60% were female. Nearly 70% of patients experienced pain in the V2 and/or V3 dermatomes, predominantly on the right side (60%). Most patients had modified BNI Pain Intensity Scale grade IV or V pain (89.2%) and were taking 1 or 2 pain medications (74.1%). The median prescription dose was 80 Gy (range 62.5-95 Gy). The proximal trigeminal nerve was targeted in 77.9% of cases, and the median follow-up was 21 months (range 6-156 months). Initial pain relief (modified BNI Pain Intensity Scale grades I-IIIa) was noted in 81.8% of evaluable patients at a median of 30 days. Of 709 patients who achieved initial pain relief, 42.3% experienced at least one pain recurrence after GKRS at a median of 44 months, with 49.0% of these patients undergoing a second procedure. New-onset facial numbness occurred in 25.3% of patients after a median of 8 months. Age ≥ 63 years was associated with a higher probability of both initial pain relief and maintaining pain relief. A distal target location was associated with a higher probability of initial and long-term pain relief, but also a higher incidence of sensory dysfunction. BED ≥ 2100 Gy2.47 was predictive of pain relief at 30 days and 1 year for the distal target, whereas physical dose ≥ 85 Gy was significant for the proximal target, but the restricted range of BED values in this subgroup could be a confounding factor. A maximum brainstem point dose ≥ 29.5 Gy was associated with a higher probability of bothersome facial numbness. CONCLUSIONS:BED and physical dose were both predictive of pain relief and could be used as treatment planning goals for distal and proximal targets, respectively, while considering maximum brainstem point dose < 29.5 Gy as a potential constraint for bothersome numbness.
PMID: 38364220
ISSN: 1933-0693
CID: 5636012